Psychedelic medicine: Mind bending, health giving

Psychedelic medicine: Mind bending, health giving
Johm Horgan, New Scientist 2005

JOHN HALPERN clearly remembers what made him change his mind about psychedelic drugs. It was the early 1990s and the young medical student at a hospital in Brooklyn, New York, was getting frustrated that he could not do more to help the alcoholics and addicts in his care. He sounded off to an older psychiatrist, who mentioned that LSD and related drugs had once been considered promising treatments for addiction. "I was so fascinated that I did all this research," Halpern recalls. "I was reading all these papers from the 60s and going, whoa, wait a minute! How come nobody's talking about this?"

More than a decade later, Halpern is now an associate director of substance abuse research at Harvard University's McLean Hospital and is at the forefront of a revival of research into psychedelic medicine. He recently received approval from the US Food and Drug Administration (FDA) to give late-stage cancer patients the psychedelic drug MDMA, also known as ecstasy. He is also laying the groundwork for testing LSD as a treatment for dreaded super-migraines known as cluster headaches.

And Halpern is not alone. Clinical trials of psychedelic drugs are planned or under way at numerous centres around the world for conditions ranging from anxiety to alcoholism. It may not be long before doctors are legally prescribing hallucinogens for the first time in decades. "There are medicines here that have been overlooked, that are fundamentally valuable," says Halpern.

These developments are a remarkable turnaround. Scientists first became interested in psychedelic drugs - also called hallucinogens because of their profound effect on perception - after Albert Hofmann, a chemist working for the Swiss pharmaceutical firm Sandoz, accidentally swallowed LSD in 1943. Hofmann's description of his experience, which he found both enchanting and terrifying, spurred scientific interest in LSD as well as naturally occurring compounds with similar effects: mescaline, the active ingredient of the peyote cactus; psilocybin, found in magic mushrooms; and DMT, from the Amazonian shamans' brew ayahuasca.

At first, many scientists called these drugs "psychotomimetics" because their effects appeared to mimic the symptoms of schizophrenia and other mental illnesses. However, many users rhapsodised about the life-changing insights they achieved during their experiences, so much so that in 1957, British psychiatrist Humphry Osmond proposed that the compounds be renamed "psychedelic", from the Greek for "mind-revealing". The term caught on, and psychiatrists started experimenting with the drugs as treatments for mental illness. By the mid-1960s, more than 1000 peer-reviewed papers had been published describing the treatment of more than 40,000 patients for schizophrenia, depression, alcoholism and other disorders.

A prominent member of this movement was Harvard psychologist Timothy Leary, who among other things tested whether psilocybin and LSD could be used to treat alcoholism and rehabilitate convicts. Although his studies were initially well received, Leary eventually lost his reputation - and his job - after he began touting psychedelics as a hotline to spiritual enlightenment. Leary's antics helped trigger a backlash, and by the late 1960s psychedelics had been outlawed in the US, Canada and Europe. Unsurprisingly, clinical research ground to a halt, partly because obtaining the necessary permits became much more difficult, but also because few researchers were willing to risk their reputations studying demonised substances.

But to some brave souls, psychedelic medicine never lost its allure. One of them is Rick Doblin, who in 1986 founded the Multidisciplinary Association for Psychedelic Studies (MAPS) in Sarasota, Florida, and who earned a doctorate from Harvard's Kennedy School of Government after writing a dissertation on the federal regulation of psychedelics. For nearly 20 years MAPS has lobbied the FDA and other government agencies to allow research on psychedelics to resume. It has also persuaded scientists to pursue the work and raised funds to support them. A similar body, the Heffter Research Institute in Santa Fe, New Mexico, was founded in 1993 by scientists with an interest in hallucinogens.

In the past couple of years their efforts have begun to pay off. Doblin is optimistic that psychedelic research is back for good, and this time it will do things right. "This gives us the chance to show that we have learned our lessons," he says. Halpern, too, is anxious to lay to rest the ghost of Leary. "That man screwed it up for so many people," he says.

With this in mind, Halpern says the first task for him and others is to evaluate the safety of psychedelics. And they are up against an entrenched orthodoxy: a 1971 editorial in The Journal of the American Medical Association warned that repeated ingestion of psychedelics causes personality deterioration. "Only a few of those who experience more than 50 'trips' are spared," it warned.

I was reading all these papers from the 60s and going, whoa, wait a minute! How come nobody's talking about this?
So Halpern's first big foray into psychedelic research was aimed at risk-assessment. In the late 1990s he launched a study of members of the Native American Church, who are permitted by US law to consume peyote. Halpern examined 210 residents of a Navajo reservation in the south-west US, who fell into three categories: church members who had taken peyote at least 100 times but had had little exposure to other drugs or alcohol; non-church members who abstained from alcohol or drugs; and former alcoholics who had been sober for at least three months.

Halpern tested the subjects' IQ, memory, reading ability and other functions. His interim results showed that church members had no cognitive impairment compared with the abstainers, and scored significantly better than recovering alcoholics. Church members also reported no "flashbacks" - sudden recurrences of a psychedelic's effects long after the initial trip. Halpern believes this study, which he expects will be published soon, shows that contrary to the 1971 editorial, peyote at least can be taken repeatedly without adverse effects.

He is now conducting a similar assessment of MDMA. This drug is sometimes called an "empathogen" because it heightens feelings of compassion and reduces anxiety. Anecdotal reports suggest it has therapeutic potential, and some psychiatrists used it alongside psychotherapy before it was outlawed in 1985. However, anecdotal and scientific evidence have also linked MDMA with brain damage, though the research is controversial.

Ecstasy impact
Judging the true impact of MDMA is complicated by the fact that users often combine it with other drugs and alcohol. To get around this, Halpern recruited a group of American mid-westerners who admitted taking MDMA but said they shunned other substances. He separated them into "moderate" users, who had consumed MDMA 22 to 50 times, and "heavy" users, who had taken it more than 50 times.

Halpern recently reported in the journal Drug and Alcohol Dependence that, compared with controls, heavy users displayed "significant deficits" in mental processing speed and impulsivity. Moderate users, however, had no major problems. Halpern believes this shows that MDMA's benefits may outweigh its risks for certain patients. And apparently the FDA and the McLean Hospital agree, since both have approved Halpern's plan to test MDMA as an anti-anxiety drug for a dozen late-stage cancer patients. Halpern still needs permission from the Drug Enforcement Administration, but he expects to begin recruiting patients soon.

He is also interested in the potential benefits of the true hallucinogens. In 1996, he reviewed almost 100 substance abuse trials involving LSD, psilocybin, DMT and ibogaine, an extract of the African shrub Tabernanthe iboga. Halpern found tentative evidence that the drugs can reduce addicts' cravings during a post-trip "afterglow" lasting for a month or two. Exactly how this happens is something of a mystery. A popular theory is that the benefits stem from the drugs' psychological effects, which include profound insights and cathartic emotions, but Halpern suspects that there may be a biochemical explanation too.

For now, however, Halpern isn't planning to pursue addiction therapy. He is more interested in another medical use for LSD and psilocybin: treating a debilitating condition known as cluster headaches. These attacks appear to be caused by swelling of blood vessels in the brain and are worse than migraines. Sufferers say the pain exceeds that of passing a kidney stone or giving birth without anaesthetics. They affect about 3 in every 1000 people sporadically, and 1 in 10,000 chronically. "There's a tremendous potential need for this," says Halpern, who investigated the problem after being approached by a patient group.

Many patients get little or no relief from painkillers, but some claim that small doses of LSD or psilocybin can alleviate the headaches and even prevent them from occurring. Halpern was intrigued; LSD is chemically related to ergot, a naturally occurring compound that constricts blood vessels, and the derivatives ergotamine and methysergide are commonly prescribed for migraines.

Halpern and his Harvard colleague Andrew Sewell are now gathering evidence to persuade licensing officials - and themselves - that LSD and psilocybin merit a clinical trial. Sewell has gathered more than 60 testimonials from cluster headache sufferers who have treated themselves with LSD or psilocybin.

Another member of the vanguard in the psychedelic revival is Charles Grob, a psychiatrist at the Harbor-UCLA Medical Center in Los Angeles, California, and co-founder of the Heffter Institute. After years struggling to get permits, Grob says he is slowly moving forward with a study into using psilocybin to reduce distress in terminal cancer patients. He points out that studies done in the 1960s suggested that psychedelics can help patients come to terms with their impending death. So far Grob has treated three patients, but he hopes to enrol more subjects shortly.

Grob has also led several investigations like Halpern's peyote study, but looking at ayahuasca, the DMT-rich shamanic brew. Ayahuasca often causes nausea and diarrhoea, and its psychedelic effects can be terrifying, but Amazonian shamans nonetheless prize it for its visionary properties. Since 1987 it has been a legal sacrament for several churches in Brazil, the largest of which is União Do Vegetal. UDV combines elements of Christianity with nature worship, and claims 8000 members.

In 1996 a team led by Grob reported in the Journal of Nervous And Mental Disease that UDV members who regularly took ayahuasca were on average physiologically and psychologically healthier than a control group of non-worshippers. The UDV followers also had more receptors for the neurotransmitter serotonin, which has been linked to lower rates of depression and other disorders. Many of the UDV members told the scientists that ayahuasca had helped them overcome alcoholism, drug addiction and other self-destructive behaviours.

Addicts often end up filled with revulsion for their past lives and determined to change
More recently, Grob has found that adolescents who grew up participating in ayahuasca ceremonies showed no ill effects and were less likely to engage in crime and substance abuse than members of a control group. Of course, Grob acknowledges that they could be benefiting from the social effects of membership in a church as well as the effects of ayahuasca itself. Grob plans to publish these results this year.

Several other scientists are quietly pursuing psychedelic research. Since 2001, psychiatrist Francisco Moreno of the University of Arizona in Tucson has been testing psilocybin as a treatment for obsessive-compulsive disorder. Psychotherapy and antidepressants such as Prozac help many patients, but some have such severe symptoms and are so resistant to treatment that they turn to electroshock therapy and even brain surgery. As with the work on cluster headaches, Moreno's study was motivated by reports from people with OCD that psilocybin relieves their symptoms.

So far, Moreno has given both sub-psychedelic and psychedelic doses of pure psilocybin to nine treatment-resistant OCD subjects, in a total of 29 therapy sessions. His preliminary findings suggest firstly that it is safe to ingest psilocybin, which was a primary concern of the trial. Beyond that, Moreno calls his results "promising", but won't discuss them further, since he plans to submit a paper to a peer-reviewed journal this year.

By the mid-1960s, over 1000 papers had been published describing psychedelic therapy
Meanwhile in Charleston, South Carolina, physician Michael Mithoefer is carrying out a MAPS-sponsored clinical trial of MDMA as a treatment for post-traumatic stress disorder. PTSD affects up to 20 per cent of people who experience a traumatic event, and involves distressing symptoms such as nightmares and panic attacks. Conventional treatments typically consist of cognitive therapy and antidepressants, but many patients don't respond to these. In the past year Mithoefer has given "MDMA-assisted" psychotherapy to six treatment-resistant patients, all traumatised by violent crimes; he plans to treat 20 patients in all.

The longest-running psychedelic therapy programme started almost 20 years ago in Russia. Evgeny Krupitsky, a psychiatrist who heads a substance-abuse clinic in St Petersburg, has treated more than 300 alcoholics and about 200 heroin addicts with ketamine. Used primarily in veterinary medicine, ketamine is an anaesthetic that can trigger an extremely disorienting hallucinogenic episode lasting an hour or so. Krupitsky's subjects often emerge from their sessions filled with revulsion for their past lives and determined to change. The therapists encourage these feelings with tricks such as forcing the subjects to sniff a bottle of vodka at the peak of their session; the patients' disgust often persists long after the ketamine's effects have worn off.

In one of Krupitsky's studies, 73 out of 111 alcoholics stayed dry for at least a year after their session, compared with 24 per cent of those in a control group. Yet his programme, which was funded by MAPS and the Heffter Institute, was recently shut down because the Russian government tightened restrictions on ketamine. Although Krupitsky says he and his colleagues "are in the process of getting permission to continue", it may be several years before research resumes.

Although disappointed by this setback, Doblin is encouraged by developments elsewhere. He is lobbying officials in Spain and Israel to approve studies of MDMA for PTSD, and is raising funds for a substance-abuse trial of ibogaine outside the US together with the Heffter Institute. MAPS has also supported Frans Vollenweider, a psychiatrist at the University of Zurich in Switzerland, who has done basic research on the physiological effects of psilocybin and MDMA, and hopes to begin clinical research soon.

Doblin's primary goal is to see psychedelics legally recognised as medicines. But he also hopes that someday healthy people may take these substances for psychological or spiritual purposes, as members of the Native American Church and União Do Vegetal do, and as he did in his youth. After all, drugs such as Prozac and Viagra are already prescribed not just to heal the ill but also to enhance the lives of the healthy.

It is still an uphill struggle. Government funds for psychedelic studies are hard to come by, and drug companies have shown absolutely no interest in supporting the research. But there are signs that the wind is changing. Although psychedelics are still classified in the US as schedule-1 drugs, and so are banned for all non-research purposes, in November a US Federal Appeals Court in Colorado ruled that a branch of the UDV based in Santa Fe, New Mexico, could import ayahuasca for use in ceremonies. Among the research findings cited in the court decision were Grob's studies showing no ill effects from ayahuasca. The Department of Justice is appealing the decision, but if the Supreme Court denies the appeal, UDV members in the US will be able to ingest ayahuasca legally.

Maybe, just maybe, after more than 30 years in the wilderness, this powerful, misunderstood but potentially mind-healing class of drugs is ready to be rehabilitated.

http://www.newscientist.com/article/mg18524881.400-psychedelic-medicine-mind-bending-health-giving.html?full=true

Dr. Rick Doblin - MAPS

Transcendental Medication

A look inside the local nonprofit that has set out to prove psychedelic drugs like ecstasy and LSD can help restore mental health. Do the benefits outweigh the dangers?The notion of psychedelic substances having medicinal or therapeutic value is far from new: For centuries, indigenous people have been chewing psychoactive cactus flesh as a cure for such ailments as toothache, fever and skin disease. And since at least as far back as the mid-19th century, members of tribes throughout the Amazon Basin have been drinking the mind-altering brew ayahuasca and purging themselves of longtime mental, emotional and physical ills. However, for modern-day Americans raised on horror stories of kids being carried off the dance floor on stretchers or plummeting to their deaths while trying to fly, such a concept can be hard to swallow. Alternately, if the mention of drugs like LSD, ecstasy and psilocybin mushrooms fills your head with images of people named Carob and Bhakti lounging on pillows and painting each other’s bellies with organic hot fudge, you might dismiss the idea of psychedelic therapy as the wishful thinking of New Age drug enthusiasts.

In truth, it’s the other way around: Many of these substances began as therapeutic drugs before people started using them recreationally. For example, scientific studies conducted in the late ’50s and early ’60s showed LSD to have great promise as an aid to the treatment of disorders like alcoholism, drug addiction, sociopathology, criminal psychopathology, sexual deviance and anxiety or depression related to terminal illness. Complications set in when vast segments of the counterculture answered former psychedelic therapy researcher Timothy Leary’s call to “turn on” in the early and mid-’60s. The clinical and recreational use of the drug were quickly outlawed, prompting Sen. Robert Kennedy to comment at a 1966 congressional hearing, “Perhaps to some extent we have lost sight of the fact that [LSD] can be very, very helpful in our society if used properly.” History repeated itself in the early ’80s, when more than a thousand U.S. psychotherapists were using MDMA (better known as ecstasy) in such endeavors as couples therapy and clinical depression treatment, claiming that it facilitated communication and allowed its users to examine their problems with significantly reduced fear. Largely through the evangelizing of former seminary student and self-proclaimed “ecstasy missionary” Michael Clegg, word soon spread that this remarkable compound had some desirable properties beyond the therapeutic. Once again, the law stepped in: In spite of a recommendation from Drug Enforcement Agency (DEA) Administrative Law Judge Francis Young that the drug remain legal for medical use by physicians, both the therapeutic and recreational use of the drug were banned in 1985.The illegality of these substances hasn’t stopped psychedelic therapy research, but it has forced such studies to go underground. To this day, there are several full-time psychedelic therapists and many more therapists who occasionally work with psychedelics, all of them risking the gravest of consequences if they’re caught.Here in Santa Cruz, however, there’s a psychedelic therapy organization that’s operating completely above ground. MAPS (Multidisciplinary Association for Psychedelic Studies), an IRS-approved nonprofit working to legalize the therapeutic use of psychedelic drugs and marijuana, is legally researching the use of not only MDMA for the treatment of Post-Traumatic Stress Disorder (PTSD), but also LSD and psilocybin (the active ingredient in psychedelic mushrooms) for the treatment of end-of-life anxiety, and the psychedelic alkaloid ibogaine as a possible cure for drug addiction. If these trials prove successful, these long-dreaded drugs could become highly valued, government-approved prescription medicines.
MAPS founder Rick Doblin
MAPS president Rick Doblin founded the organization in 1986 after of working for a couple of years with the nonprofit group Earth Metabolic Design Laboratories to block the DEA from criminalizing the therapeutic use of MDMA. Doblin, a graduate of Harvard’s Kennedy School of Government, holds a doctorate in Public Policy relating to the regulation of the medical use of psychedelics and medical marijuana. “What I was able to do over those years [of study] is come to a pretty clear understanding of the political obstructions and forces that were working on both sides: to try to continue to suppress this research or to try to bring it to the surface,” he explains. Armed with this knowledge, he developed an organization that would “channel the people’s hopes that these drugs could become more accepted, not underground, and make a major contribution to society.”Though the MAPS office and the majority of the organization’s staff members are located in Santa Cruz (for fear of attracting hangers-on seeking free drugs, they prefer that we not print their address), Doblin himself resides in Boston, while MAPS research and information specialist Ilsa Jerome, Ph.D. lives in Somerville, Mass. Doblin and Jerome work as a team with Santa Cruz staff members Valerie Mojeiko (director of operations), Randolph Hencken, M.A., B.S. (director of communications and marketing), Josh Sonstroem (accounting and IT) and Jalene Otto (membership and sales coordinator) by way of what Doblin refers to as “the miraculous technology of the 21st century.” In explanation of MAPS’ therapeutic approach, which is built on the work of the world’s leading LSD therapist, Stanislav Grof, M.D. (under whom Doblin studied a psychotherapeutic technique called holotropic breathwork from 1987 to 1990), Doblin comments, “When your body gets cut, you clean up the wound, and the body has this innate healing property: It tries to build the skin back together and recreate a whole, intact body. We feel like the psyche is the same: There are these innate healing capacities in the psyche, but sometimes they go awry, so if we can remove some of these impediments, which are often defenses against these powerful feelings, [healing can occur].”
Rick Doblin developed an organization that would “channel the people’s hopes that these drugs could become more accepted, not underground, and make a major contribution to society.”
The Agony and the Ecstasy
Doblin sees MDMA as the first psychedelic likely to be approved for therapeutic use due to the fact that with adequate support, people who have never taken drugs before can handle it, whereas the other psychedelics are more challenging. For this reason, the bulk of MAPS’ research is MDMA-based.On a strictly biological level, MDMA reduces activity in the amygdala, a section of the brain that mediates the automatic fear response, while increasing activity in the ventromedial prefrontal cortex, which regulates emotional control. The result is that the MDMA taker is able to lower his or her defenses enough to examine his/her psyche with greatly reduced anxiety. “It’s astonishing how MDMA can alter patterns that have been under way for decades,” Doblin notes. “It may very well be that this difficult work can be done in remarkably short periods of time: Sometimes in a matter of minutes, when they’re emotionally ready, [MDMA takers] work their way through it.” MAPS recently completed the first study in the world of the therapeutic use of MDMA. Twenty-one subjects between the ages of 26 and 54 took part in this FDA-approved examination of the drug’s efficacy in the treatment of Post-Traumatic Stress Disorder, which took place in Charleston, South Carolina from March 2004 to September 2008. Along with several survivors of childhood sexual abuse or rape, the participants included two veterans who had served in Iraq. Drugs were actually a fairly small part of these double-blind, placebo-controlled trials: During the four months of treatment that each subject underwent, he or she only took MDMA on three different days, scheduled a month apart from each other. Multiple non-drug psychotherapy sessions preceded the first MDMA session, helping the patient to prepare for the experience in order to take maximum advantage of it, and the subject received daily therapy sessions for a week after each MDMA session to help him/her to integrate it. Overseeing these intense and often painful MDMA sessions were psychiatrist Michael Mithoefer, M.D., and his wife, psychiatric nurse Ann Mithoefer, B.S.N. In what Michael describes as a very comfortable, aesthetically pleasing office, the subject would take a capsule at about 10 a.m., not knowing whether it was MDMA or a placebo, and lie on a futon with the therapists on either side of him or her. A self-running machine measured the subject’s blood pressure every 15 minutes, thereby minimizing physical danger. All sessions were audiotaped and videotaped for patient review and to help MAPS perfect its method. Unless the patient requested otherwise, music was played to help “drive, amplify and calm the emotions,” as Doblin puts it. Approximately half of the eight-hour MDMA therapy session was spent in silence as the subject allowed various feelings and emotions to arise, and the other half was spent in therapeutic conversation. Doblin claims that under the influence of MDMA, many patients remembered long-forgotten details of traumatic events. He adds that he and other staff members have talked to a great many people who have taken MDMA at raves or parties and spontaneously remembered sexual assaults or other traumatic experiences they’d previously blocked out of their minds. If the MDMA taker is surrounded by supportive people during such an incident, it can be a deeply healing experience, but all too often, she or he is surrounded by partiers who don’t want to be “brought down.” In a situation specifically designed to let the MDMA taker work through his or her trauma, however, the patient is not only permitted but encouraged to let it all out. “There will be different moments of crying, perhaps catharsis, fear, anxiety, of letting in these strong, strong emotions that have been plaguing people sometimes for 30, 40 years,” Doblin says. “Things at times will, from the outside, be looking like they’re getting worse: People can be shaking with terror, vomiting from nausea, crying, sobbing, but there’s a healing quality to all of that when people are processing emotions and feelings that have been stored for so long.”This pilot study’s success rates are impressive indeed: Only 15 percent of the subjects who were given MDMA capsules still met the criteria for PTSD after treatment, as opposed to 85 percent of the people who were given placebos. Making these statistics all the more remarkable is the fact that the only people allowed to participate in the study were treatment-resistant: They’d failed to obtain relief from long-term psychotherapy or from the FDA-approved medications for PTSD. “These are preliminary results, and it’s a small study, but it’s certainly encouraging,” Dr. Mithoefer offers.Doblin says if the patient has responded well to the treatment, he or she no longer needs any drugs for PTSD, be they MDMA, Zoloft or Paxil. He adds that out of the 21 patients in the pilot study, three were on permanent disability due to their trauma before taking part in the study, and all three have returned to work since being treated. “If we just think about that, what that means is that in 2004, the Veterans Administration spent $4.3 billion on disability payments to 215,000 vets,” he observes. “That’s $20,000 per year on the average. Now, that’s before a lot of people started coming back from Iraq and Afghanistan with Post-Traumatic Stress Disorder.” But does the patient come away from this therapy with a permanently heightened sense of well-being, or do the MDMA sessions merely provide fleeting tastes of freedom? Mithoefer is currently involved in a long-term follow-up study that will help answer that question. His general sense is that although maybe not everything the subjects get from the session is lasting, a significant amount of it stays with them. He stresses the importance of follow-up and integration in this process: “What we know about what [MDMA] does in the brain in terms of decreasing activity in the fear center and allowing people to have a state in which they’re able to process things is very powerful, and it shouldn’t be taken lightly, because it can stir things up. People can have more trouble afterwards, I think, if they don’t have good support and follow-up.”
“When your body gets cut, you clean up the wound, and the body has this innate healing property: It tries to build the skin back together and recreate a whole, intact body. We feel like the psyche is the same: There are these innate healing capacities in the psyche, but sometimes they go awry, so if we can remove some of these impediments, which are often defenses against these powerful feelings, [healing can occur].” —Rick Doblin
Bad Medicine?
Leaving aside any psychological difficulty that might follow an MDMA experience, we come to the thorny issue of the drug’s well-publicized physical dangers, such as the risk of death by hyperthermia when a recreational ecstasy user dances all night in a hot, crowded environment without stopping to cool down or rehydrate. Conversely, if he or she overcompensates by drinking huge amounts of water, it’s possible for him/her to die from brain edema due to overhydration. Complicating the matter for recreational users is the fact that as a consequence of the drug’s illegality, the MDMA may be mixed with more dangerous substances, or the taker might simply be getting another, far deadlier drug altogether. Assuming one is taking pure MDMA, however, risk of death is slim. An extremely eye-opening 2006 report by Peter Jennings (viewable here ) revealed that out of approximately 19,000 deaths reported to New York City’s Medical Examiner’s office over a period of about three years, only 22 of the deceased had ecstasy in their systems, and only two died from ecstasy alone. According to the DEA, during those three years, New Yorkers used about 110 million doses of ecstasy. Doblin claims that death by MDMA is a one-in-a-million case, adding that a few years ago, MAPS did a statistical comparison of the risks of taking MDMA with those of cheerleading, with cheerleading proving to be the more dangerous activity. Both Mithoefer and Doblin hold that in a controlled environment such as the MDMA therapy study, where the subjects are being monitored and given a proper amount of fluids, the physical risks are extremely low. Helping to further minimize the danger, subjects are also screened for medical problems due to the fact that MDMA causes its taker’s blood pressure and pulse to go up considerably. (This isn’t dangerous for a healthy person, but it could prove problematic for someone with heart disease or cerebrovascular disease.) Along with the threat of death, MDMA is often associated with brain damage. Many of these fears stem from a government-funded study led by neurologist George Ricaurte, M.D., Ph.D. of Baltimore’s Johns Hopkins Medical Institution. Published in the medical journal The Lancet in 1998, this report stated that ecstasy users risk losing up to 85 percent of the brain’s serotonin function. An unforgettable image associated with that study—the cranial PET scan of a woman who had supposedly put holes in her brain by taking a huge amount of MDMA—became a powerful weapon in an anti-ecstasy crusade led by the National Institute on Drug Abuse (NIDA). Space limitations prohibit a full account of the many ways in which that image and the study from which it was supposedly derived have been exposed as fraudulent, but interested parties are encouraged to look up the April 2002 New Scientist article “Ecstasy on the Brain” (http://mdma.net/misc/ecstasy-mdma.html), the December 2003 New York Times article “Research on Ecstasy is Clouded by Errors” (nytimes.com/2003/12/02/science/02ECST.html) and a German study of the effects of MDMA on serotonin levels, published in The Journal of Nuclear Medicine in 2003 (Link ). Four years after the publication of the discredited Johns Hopkins study, at a time when fears of MDMA-induced serotonin depletion were waning, Ricaurte returned with a new MDMA study: This time he published a paper in the journal Science claiming that MDMA caused severe damage to the brain’s dopamine system and that a single, standard-sized recreational dose of ecstasy could cause Parkinson’s disease. After Science asked Ricaurte to respond to letters to the editor from MAPS staff that challenged these assertions, Ricaurte and his team were unable to replicate the results of their study, even after giving larger and larger doses of MDMA to the monkeys being studied and increasing the temperature of the room to increase neurotoxicity. In a scandal that severely tarnished the anti-MDMA movement’s credibility, it ultimately came to light that the monkeys had not been given MDMA in the original study, but methamphetamine. Along with being far more toxic than MDMA, methamphetamine is potent at much lower doses than MDMA (“Even 10 grams can be a lot,” Doblin notes) and has been shown to be harmful to dopamine. The Johns Hopkins researchers subsequently issued a full retraction of the article, admitting that all but one of the monkeys were accidentally injected with methamphetamine rather than MDMA. In his retraction letter to Science, Ricaurte blamed this discrepancy on a labeling error on the part of his chemical supplier, RTI International, which was overseen by the DEA. Surprisingly, Doblin himself helped recruit volunteers and arrange the financing for Dr. Ricaurte’s studies. If this seems curious at first glance, it becomes less so in light of Doblin’s belief that with the government exaggerating the risks and denying the benefits of MDMA use, MAPS has to be careful not to do the opposite. “We try to be very careful about what we claim to be the benefits, and we try to design the best research studies possible looking into the risks of MDMA,” he states. “So there seems to be pretty much nothing to worry about. Certainly, in a therapeutic context, there is nothing to worry about in terms of neurotoxicity or functional consequences.”The functional consequences to which Doblin refers are mainly memory-related. Mithoefer states that there may be some evidence that taking high doses of MDMA frequently may cause memory problems for some people. “I think the jury is still out [on the issue of memory problems] in some ways, but we did neuropsychological testing before and after [the MDMA therapy sessions] and found no evidence of memory problems,” he offers. “When this dose is taken two or three times in a controlled setting, it doesn’t look like there’s a high probability of it causing any memory problems.” A five-year, $1.8 million government-funded study that MAPS helped start is currently under way at Harvard Medical School. Scheduled to end in September, this study examines a population of people whose drug use has been limited almost exclusively to ecstasy. By Doblin’s account, the research so far has shown that in terms of memory, there are no substantial differences between people who have taken ecstasy and people who have never taken drugs. The results of this research should not be taken as proof that there are no adverse consequences of recreational ecstasy use, but they do seem to indicate that the drug is reasonably safe for therapeutic use. “We’ve now been able to show through scientific research that these claims of risk are vastly exaggerated, that the denial of the benefits is completely wrong, and that really, we’re sitting on something that’s going to be making a major contribution to the psychiatry and psychotherapy of the future,” Doblin declares.
Health Trip
Along with various other studies of the treatment of PTSD with MDMA (including clinical trials in Switzerland, Israel, Canada and Jordan), MAPS is sponsoring a 12-subject trial in Switzerland examining the use of LSD in the treatment of clinical anxiety associated with life-threatening illness. Expected to be completed in the fall of 2010, this is the first study of LSD as a therapeutic aid in more than 35 years. Also currently under development is a study of psilocybin-assisted therapy in the treatment of end-of-life anxiety, to be held in an as-yet-undecided U.S. location, and an inquiry into the use of ibogaine in the treatment of opiate addiction, taking place in Playas de Tijuana, Mexico. Because the effects of these other psychedelics are more unpredictable and more difficult to steer than those of MDMA, using such substances in a therapeutic context is a bit more challenging. “People require more support, more preparation, and it takes sometimes a lot more time spent negotiating with one’s defenses when you’re working with the classic psychedelics,” Doblin says. “But they still have this feeling that there’s something inherently healing about this emergence.” According to the rules of FDA-approved research, MAPS is currently required to research these drugs one at a time, but there’s more and more talk among MAPS staff members of combining MDMA and LSD in therapy sessions, with the former helping to take some of the edge off the latter. Such a combination might prove especially useful in the treatment of PTSD, where caution needs to be taken to avoid re-traumatizing the subjects rather than helping them heal.In spite of the delicate nature of giving psychedelic drugs to people suffering from trauma, Doblin claims that given a safe, supportive environment and adequate preparation, the study subjects may do a lot of grappling, but they can generally handle the experience. “It just takes a lot of work and courage to get to the point where one opens to it,” he says.
“The federal government has a monopoly on the supply of marijuana, and has for the last 40 years hindered research into making marijuana into a prescription medicine.”—Rick Doblin
Pipe Dreams?
Perhaps the most challenging of MAPS’ efforts is its ongoing push for legalization and FDA approval of marijuana as a prescription medicine. “The federal government has a monopoly on the supply of marijuana and has for the last 40 years hindered research into making marijuana into a prescription medicine,” Doblin asserts. MAPS has been wrestling with this issue since 1990, when its staff conducted a survey comparing smoked marijuana with the oral THC pill as used in cancer therapy. The organization also worked throughout the ’90s with UCSF’s Dr. Donald Abrams to start a study of the use of medical marijuana in HIV-positive patients as well as with Montana State University’s Dr. Ethan Russo to start a study of the use of cannabis for the treatment of migraines, only to find its efforts blocked by NIDA. MAPS, which has also been working with California NORML (National Organization for the Reform of Marijuana Laws) since 1993 to sponsor research on the use of vaporizers and water pipes as a means of reducing the physically damaging effects of smoking cannabis, has been unsuccessfully attempting to purchase marijuana from NIDA for more research in this area since June 2003.MAPS is now attempting to get an FDA license for a medical marijuana farm at UMass-Amherst in order to produce marijuana that would be acceptable for use in FDA studies. Six days before Obama took office, the DEA rejected a recommendation by its own Administrative Law Judge, Mary Ellen Bittner, who, after extensive hearings, recommended approval of the license. MAPS staff members are presently waiting to find out if they’ll be given a chance to appeal this decision. According to Doblin, with the DEA still under old leadership appointed by former President George Bush, MAPS hopes to continue its legal struggles long enough for new leadership to come into the DEA. If not, Plan B is to sue the DEA through the First Circuit Court of Appeals.

Research on psychedelics moves into the mainstream

Research on psychedelics moves into the mainstream

Kelly Morris

The Lancet

Volume 371, Issue 9623, 3 May 2008-9 May 2008, Pages 1491-1492

The backlash against the recreational use of psychedelic drugs in the 1960s had a negative effect on research into their potential therapeutic benefit. But now attitudes are changing and work in this area is being revitalised, with several early-stage trials underway. Kelly Morris reports.

Some 50 years ago, substances called psychedelics were hailed as the new tools of psychiatry. After their use in diverse clinical contexts, not always with rigorous methods, and following widespread non-medical use, “research was quashed for misguided but understandable reasons”, explains Rick Doblin, president of the US Multidisciplinary Association for Psychedelic Studies (MAPS). Now, that scenario is rapidly changing, with several phase II trials underway worldwide, and many more studies ongoing or planned. “It's amazing how much is going on”, Doblin told The Lancet after the World Psychedelic Forum that took place in Basel, Switzerland at the end of March.

Part of this resurgence, say experts, is down to a more measured attitude of researchers towards the risks and the benefits of drugs like lysergide (LSD), psilocybin, and methylenedioxymethamfetamine (MDMA). “What we see now is the [US] FDA (Food and Drug Administration) making decisions based on data rather than politics, and major universities involved in research”, notes Tom Roberts, a professor of educational psychology from Northern Illinois University, IL, USA, and co-editor of the book Psychedelic Medicine. Clinical studies are the most appropriate context to start re-exploring the use of psychedelics, says Roberts, because of rigorous review processes and the step-by-step development of studies. The “Timothy Leary era” of informal or illegal explorations “caused a lot of problems”, he notes. Ben Sessa, a consultant psychiatrist based in the UK, agrees. “At the end of the 1960s these drugs were labelled as dangerous drugs of abuse in the wake of the explosion of recreational use by the general public. The resulting war on drugs has been only minimally effective at tackling recreational use but has been extremely damaging for any genuine medical research”, he says.

What the experience of the 1960s has shown is pointers to many possible therapeutic and non-medical uses. “The evidence so far suggests that the anxiety (neurotic) disorders tend to do well with psychedelics—that includes anxiety, post-traumatic stress disorder, and obsessive-compulsive disorder. This is because these drugs are particularly good at allowing the user to access otherwise repressed and painful memories and do some meaningful psychotherapeutic work under the influence of the drug”, says Sessa. Previous clinical experience, plus more recent informal use, has indicated other potential therapeutic uses for cluster headaches and addictions, among other conditions.

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The therapeutic benefit of MDMA is being tested in pilot studies for post-traumatic stress disorder

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Some of the first clinical trials have focused on MDMA, which is not a classic hallucinogen. Doblin was keen to develop protocols for formal phase II studies given the drug's reported capacity “to enhance people's ability to feel, accept, and integrate difficult emotions” within a psychotherapeutic context. Of MAPS' three pilot studies for post-traumatic stress disorder worldwide, the US study ends first, in July. Three further phase II studies are in planning. “What we need to do is to replicate the US findings”, says Doblin, who then hopes to see the development of phase III trials in Europe and the USA, which, if positive, could pave the way for MDMA to be available as a prescription medicine.

“We have shown that LSD [historically] and MDMA given in a psychotherapeutic context can be safe”, notes Doblin, but he emphasises that the therapeutic outcome seems highly dependent on the therapeutic context. Thus, as Roberts explains, “in psychotherapeutic sessions, psychedelics are best thought of as adjuncts to psychotherapy, not as whole treatments themselves”. Doblin concurs: “We are talking about reversing a lifetime of patterns, in some cases, so the magic bullet or single-dose miracle cure theory is out the window. Multiple doses are needed in the context of long-term psychotherapy.”

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Psychedelics might be of benefit in the treatment of cluster headaches

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Now, the first clinical trial of psilocybin in terminal cancer patients led by Charles Grob at the University of California is nearing completion, and others are recruiting or about to start further investigating psilocybin, MDMA, or LSD in similar situations. For example, a study led by Stephen Ross and Anthony Bossis from the New York University School of Medicine, NY, USA, is about to commence using psilocybin with psychological support, with endpoints that include reductions in anxiety, depression, pain, and increased acceptance of death. “I am interested in novel ways to relieve suffering for end-of-life cancer patients”, says Bossis. “We are looking to determine whether a mystical state can alleviate the psychosocial and existential anxiety associated with the end of life.” Roland Griffiths from Johns Hopkins University School of Medicine, Baltimore, MD, USA, is also researching the effect of psilocybin on anxiety surrounding cancer diagnosis; this trial is unique in that patients with and without disease progression will be eligible.

Amanda Neidpath, director of the UK Beckley Foundation, has been working for years to initiate new research on LSD, by collaborating with various groups worldwide. In addition to therapeutic research, she believes “we need to understand the mechanisms by which we get these changes of perception that may be beneficial…how these substances work, how they are helpful, and for whom”. Also, since psychedelics would not be efficacious in everyone, an understanding of mechanisms may point to non-psychedelic means to achieve the same therapeutic effects. Research on mechanisms might also help explore other potential uses for psychedelics. One such study about to commence will investigate the effects of LSD on brain connectivity and sensory processing, which might clarify previous suggestions about how psychedelics might enhance cognition and creativity.

“As our view of the human mind and nervous system expands, it is being recognised that different mind-body states, different from our waking state, are also useful”, says Roberts. One such state, which has been anecdotally linked with enhanced wellbeing and anti-addictive properties, is the group use of ayahuasca. This ancient compound is not pure, but a mixture of plants used mainly by indigenous and spiritual groups. Traditional mixtures vary, but all contain a source of the psychedelic dimethyltryptamine plus a compound to prevent its gastrointestinal breakdown.

Jordi Riba and a team led by Manel Barbanoj from the Hospital de Sant Pau in Barcelona, Spain have been studying ayahuasca in healthy volunteers for about 10 years. Using a freeze-dried preparation, administered at standard doses of the active alkaloids, the team have done tolerability and pharmacokinetic studies in addition to collecting data on neuroendocrine, immune, and subjective parameters. “During the acute phase [3–4 h], volunteers reported having gone through a deeply introspective and emotional experience with thoughts usually revolving around personal concerns”, notes Riba. “Most participants found this interesting and useful, and it is in this remarkable characteristic of ayahuasca where the potential for modifying self-destructive behaviours, such as drug abuse, could reside”, he speculates. EEG and SPECT studies have confirmed changes in brain electrical activity and blood flow consistent with these subjective effects, and now the team plans to assess the effect on long-term healthy users.

In learning lessons from the 1950s and 1960s, researchers in general remain cautious about the potential for psychedelics and how they are investigated. Roberts notes that except for a study on cluster headaches (which reviewed informal use), all studies presented at the recent Basel forum specify that psychedelics are taken in the presence of a trained professional, and programmes for educating and training professionals are starting to be developed. MAPS is planning to seek FDA approval for a training programme for psychotherapists or nurses to become psychedelic psychotherapists. Ross, with Jeffrey Guss, has developed a course on psychedelic medicine, taught earlier this year to a group including medical students, psychiatry residents, and post-doctoral addiction fellows at Bellevue Hospital department of psychiatry in New York, USA. The course focuses on use of psychedelics for addiction.

The development of education in parallel with research is essential to ensure an academic focus towards psychedelic medicine, Ross and others believe. “Often people hold very passionate and pseudo-scientific opinions about these drugs on both sides of the debate. As clinicians, we need to remain dispassionate and hold true to the principles of evidence-based medicine…we owe it to those patients who may benefit from this approach”, says Sessa.